Benzyl chloroformate → (S)-1-((Benzyloxy)carbonyl)piperidine-3-carboxylic acid

HRID 1020055Notes

Reaction equation

HRID 1020055 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1.C(=O)(O)[O-].[Na+].Cl[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]>C1COCC1.O>[CH2:19]([O:18][C:16]([N:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1)=[O:17])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 6575389Nipecotic acid, S-(+)-

Product 1

HCID 736539(S)-1-((Benzyloxy)carbonyl)piperidine-3-carboxylic acidYield 49.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (S)-piperidine-3-carboxylic acid (XXXI) (10.0 g, 77.4 mmol) in a mixture of 80 ml of THF and 50 ml of water was cooled to 0° C. and sodium bicarbonate (13.0 g, 15.5 mmol) and benzyl chloroformate (15.8 g, 92.9 mmol) were added simultaneously. The reaction mixture was stirred at 0° C. for 6 hours and concentrated under reduced pressure. The aqueous layer was extracted with ethyl ether to remove excess of benzyl chloroformate, then it was acidified with 1 M HCl solution to pH 6 followed by extraction with ethyl acetate. The organic layer was separated, dried over sodium sulfate and concentrated to provide (S)-piperidine-1,3-dicarboxylic acid 1-benzyl ester (XXXII) (10.0 g, 49%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionThe aqueous layer was extracted with ethyl ether
  3. customto remove excess of benzyl chloroformate
  4. extractionfollowed by extraction with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0ed5b3b384874ffebfa866baf7fa7d51
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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